Sakai M

References (8)

Title : Hepatic FASN deficiency differentially affects nonalcoholic fatty liver disease and diabetes in mouse obesity models - Matsukawa_2023_JCI.Insight_8__e161282
Author(s) : Matsukawa T , Yagi T , Uchida T , Sakai M , Mitsushima M , Naganuma T , Yano H , Inaba Y , Inoue H , Yanagida K , Uematsu M , Nakao K , Nakao H , Aiba A , Nagashima Y , Kubota T , Kubota N , Izumida Y , Yahagi N , Unoki-Kubota H , Kaburagi Y , Asahara SI , Kido Y , Shindou H , Itoh M , Ogawa Y , Minami S , Terauchi Y , Tobe K , Ueki K , Kasuga M , Matsumoto M
Ref : JCI Insight , 8 : , 2023
Abstract : Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes are interacting comorbidities of obesity, and increased hepatic de novo lipogenesis (DNL), driven by hyperinsulinemia and carbohydrate overload, contributes to their pathogenesis. Fatty acid synthase (FASN), a key enzyme of hepatic DNL, is upregulated in association with insulin resistance. However, the therapeutic potential of targeting FASN in hepatocytes for obesity-associated metabolic diseases is unknown. Here, we show that hepatic FASN deficiency differentially affects NAFLD and diabetes depending on the etiology of obesity. Hepatocyte-specific ablation of FASN ameliorated NAFLD and diabetes in melanocortin 4 receptor-deficient mice but not in mice with diet-induced obesity. In leptin-deficient mice, FASN ablation alleviated hepatic steatosis and improved glucose tolerance but exacerbated fed hyperglycemia and liver dysfunction. The beneficial effects of hepatic FASN deficiency on NAFLD and glucose metabolism were associated with suppression of DNL and attenuation of gluconeogenesis and fatty acid oxidation, respectively. The exacerbation of fed hyperglycemia by FASN ablation in leptin-deficient mice appeared attributable to impairment of hepatic glucose uptake triggered by glycogen accumulation and citrate-mediated inhibition of glycolysis. Further investigation of the therapeutic potential of hepatic FASN inhibition for NAFLD and diabetes in humans should thus consider the etiology of obesity.
ESTHER : Matsukawa_2023_JCI.Insight_8__e161282
PubMedSearch : Matsukawa_2023_JCI.Insight_8__e161282
PubMedID: 37681411
Gene_locus related to this paper: human-FASN , mouse-FASN

Title : Draft Genome Sequences of Streptomyces scabiei S58, Streptomyces turgidiscabies T45, and Streptomyces acidiscabies a10, the Pathogens of Potato Common Scab, Isolated in Japan - Tomihama_2016_Genome.Announc_4_e00062
Author(s) : Tomihama T , Nishi Y , Sakai M , Ikenaga M , Okubo T , Ikeda S
Ref : Genome Announc , 4 :e00062 , 2016
Abstract : The draft genome sequences of the three pathogens of potato common scab, Streptomyces scabiei S58, Streptomyces turgidiscabies T45, and Streptomyces acidiscabies a10, isolated in Japan, are presented here. The genome size of each strain is >10 Mb, and the three pathogenic strains share genes located in a pathogenicity island previously described in other pathogenic Streptomyces species.
ESTHER : Tomihama_2016_Genome.Announc_4_e00062
PubMedSearch : Tomihama_2016_Genome.Announc_4_e00062
PubMedID: 26941144
Gene_locus related to this paper: strsc-a0a117ee86 , 9actn-a0a100j036 , strsc-a0a100jmt3 , strsc-a0a117ede4

Title : Glucose-independent renoprotective mechanisms of the tissue dipeptidyl peptidase-4 inhibitor, saxagliptin, in Dahl salt-sensitive hypertensive rats - Uchii_2016_Eur.J.Pharmacol_783_56
Author(s) : Uchii M , Kimoto N , Sakai M , Kitayama T , Kunori S
Ref : European Journal of Pharmacology , 783 :56 , 2016
Abstract : Although previous studies have shown an important role of renal dipeptidyl peptidase-4 (DPP-4) inhibition in ameliorating kidney injury in hypertensive rats, the renal distribution of DPP-4 and mechanisms of renoprotective action of DPP-4 inhibition remain unclear. In this study, we examined the effects of the DPP-4 inhibitor saxagliptin on DPP-4 activity in renal cells (using in situ DPP-4 staining) and on renal gene expression related to inflammation and fibrosis in the renal injury in hypertensive Dahl salt-sensitive (Dahl-S) rats. Male rats fed a high-salt (8% NaCl) diet received vehicle (water) or saxagliptin (12.7mg/kg/day) for 4 weeks. Blood pressure (BP), serum glucose and 24-h urinary albumin and sodium excretions were measured, and renal histopathology was performed. High salt-diet increased BP and urinary albumin excretion, consequently resulting in glomerular sclerosis and tubulointerstitial fibrosis. Although saxagliptin did not affect BP and blood glucose levels, it significantly ameliorated urinary albumin excretion. In situ staining showed DPP-4 activity in glomerular and tubular cells. Saxagliptin significantly suppressed DPP-4 activity in renal tissue extracts and in glomerular and tubular cells. Saxagliptin also significantly attenuated the increase in inflammation and fibrosis-related gene expressions in the kidney. Our results demonstrate that saxagliptin inhibited the development of renal injury independent of its glucose-lowering effect. Glomerular and tubular DPP-4 inhibition by saxagliptin was associated with improvements in albuminuria and the suppression of inflammation and fibrosis-related genes. Thus, local glomerular and tubular DPP-4 inhibition by saxagliptin may play an important role in its renoprotective effects in Dahl-S rats.
ESTHER : Uchii_2016_Eur.J.Pharmacol_783_56
PubMedSearch : Uchii_2016_Eur.J.Pharmacol_783_56
PubMedID: 27063445

Title : Chronic administration of DSP-7238, a novel, potent, specific and substrate-selective DPP IV inhibitor, improves glycaemic control and beta-cell damage in diabetic mice - Furuta_2010_Diabetes.Obes.Metab_12_421
Author(s) : Furuta Y , Horiguchi M , Sugaru E , Ono-Kishino M , Otani M , Sakai M , Masui Y , Tsuchida A , Sato Y , Takubo K , Hochigai H , Kimura H , Nakahira H , Nakagawa T , Taiji M
Ref : Diabetes Obes Metab , 12 :421 , 2010
Abstract : AIMS: The purpose of this study is to assess the in vitro enzyme inhibition profile of DSP-7238, a novel non-cyanopyrrolidine dipeptidyl peptidase (DPP) IV inhibitor and to evaluate the acute and chronic effects of this compound on glucose metabolism in two different mouse models of type 2 diabetes. METHODS: The in vitro enzyme inhibition profile of DSP-7238 was assessed using plasma and recombinant enzymes including DPP IV, DPP II, DPP8, DPP9 and fibroblast activation protein alpha (FAPalpha) with fluorogenic substrates. The inhibition type was evaluated based on the Lineweaver-Burk plot. Substrate selectivity of DSP-7238 and comparator DPP IV inhibitors (vildagliptin, sitagliptin, saxagliptin and linagliptin) was evaluated by mass spectrometry based on the changes in molecular weight of peptide substrates caused by release of N-terminal dipeptides. In the in vivo experiments, high-fat diet-induced obese (DIO) mice were subjected to oral glucose tolerance test (OGTT) following a single oral administration of DSP-7238. To assess the chronic effects of DSP-7238 on glycaemic control and pancreatic beta-cell damage, DSP-7238 was administered for 11 weeks to mice made diabetic by a combination of high-fat diet (HFD) and a low-dose of streptozotocin (STZ). After the dosing period, HbA1c was measured and pancreatic damage was evaluated by biological and histological analyses. RESULTS: DSP-7238 and sitagliptin both competitively inhibited recombinant human DPP IV (rhDPP IV) with K(i) values of 0.60 and 2.1 nM respectively. Neither vildagliptin nor saxagliptin exhibited competitive inhibition of rhDPP IV. DSP-7238 did not inhibit DPP IV-related enzymes including DPP8, DPP9, DPP II and FAPalpha, whereas vildagliptin and saxagliptin showed inhibition of DPP8 and DPP9. Inhibition of glucagon-like peptide-1 (GLP-1) degradation by DSP-7238 was apparently more potent than its inhibition of chemokine (C-X-C motif) ligand 10 (IP-10) or chemokine (C-X-C motif) ligand 12 (SDF-1alpha) degradation. In contrast, vildagliptin and saxagliptin showed similar degree of inhibition of degradation for all the substrates tested. Compared to treatment with the vehicle, single oral administration of DSP-7238 dose-dependently decreased plasma DPP IV activity and improved glucose tolerance in DIO mice. In addition, DSP-7238 significantly decreased HbA1c and ameliorated pancreatic damage following 11 weeks of chronic treatment in HFD/STZ mice. CONCLUSIONS: We have shown in this study that DSP-7238 is a potent DPP IV inhibitor that has high specificity for DPP IV and substrate selectivity against GLP-1. We have also found that chronic treatment with DSP-7238 improves glycaemic control and ameliorates beta-cell damage in a mouse model with impaired insulin sensitivity and secretion. These findings indicate that DSP-7238 may be a new therapeutic agent for the treatment of type 2 diabetes.
ESTHER : Furuta_2010_Diabetes.Obes.Metab_12_421
PubMedSearch : Furuta_2010_Diabetes.Obes.Metab_12_421
PubMedID: 20415690

Title : A 38 kb segment containing the cdc2 gene from the left arm of fission yeast chromosome II: sequence analysis and characterization of the genomic DNA and cDNAs encoded on the segment - Machida_2000_Yeast_16_71
Author(s) : Machida M , Yamazaki S , Kunihiro S , Tanaka T , Kushida N , Jinnno K , Haikawa Y , Yamazaki J , Yamamoto S , Sekine M , Oguchi A , Nagai Y , Sakai M , Aoki K , Ogura K , Kudoh Y , Kikuchi H , Zhang MQ , Yanagida M
Ref : Yeast , 16 :71 , 2000
Abstract : A genomic 38 kbp segment on the c1750 cosmid clone containing the cdc2 gene, located in the left arm of chromosome II from Schizosaccharomyces pombe, was sequenced. The segment was found to have five previously known genes, pht1, cdc2, his3, act1 and mei4. Among 11 coding sequences (CDSs) predicted by the gene finding software INTRON.PLOT., four CDSs, pi007, pi010, pi014 and pi016, had considerable similarity to 40S ribosomal protein, glycosyltransferase, cdc2-related protein kinase and alpha-1, 2-mannosyltransferase, respectively. Another unusually huge open reading frame (ORF) (pi011), consisting of 2233 amino acids, existed, having significant homology to alpha-amylase, granule-bound glycogen synthase and the Sz. pombe YS 1110 clone product at the N-terminal, middle and C-terminal regions, respectively. All the predicted 11 CDSs were experimentally analysed by RACE PCR. The sequencing of the RACE products revealed that there were two small overlaps at the 3' untranslated regions (UTRs) between pi004 and pi005 (17 bp) and between pi007 and pi008 (2 bp). The distances between 5' end of the 5'UTR and the putative translation initiation codon varied from 10 to 302 nucleotides (nt) among the nine CDSs successfully analysed by 5'-RACE. The expression level of each CDS on this clone was determined. Among the 16 genes on this clone, the previously determined genes, pht1, cdc2, his3 and act1, were found to be most highly expressed. Finally, cDNAs of all the newly identified genes were detected by RACE, proving the actual expression of these genes. The nucleotide sequence has been submitted to the EMBL database under Accession No. AB004534.
ESTHER : Machida_2000_Yeast_16_71
PubMedSearch : Machida_2000_Yeast_16_71
PubMedID: 10620777
Gene_locus related to this paper: schpo-be46

Title : Complete sequence and gene organization of the genome of a hyper-thermophilic archaebacterium, Pyrococcus horikoshii OT3 - Kawarabayasi_1998_DNA.Res_5_55
Author(s) : Kawarabayasi Y , Sawada M , Horikawa H , Haikawa Y , Hino Y , Yamamoto S , Sekine M , Baba S , Kosugi H , Hosoyama A , Nagai Y , Sakai M , Ogura K , Otsuka R , Nakazawa H , Takamiya M , Ohfuku Y , Funahashi T , Tanaka T , Kudoh Y , Yamazaki J , Kushida N , Oguchi A , Aoki K , Kikuchi H
Ref : DNA Research , 5 :55 , 1998
Abstract : The complete sequence of the genome of a hyper-thermophilic archaebacterium, Pyrococcus horikoshii OT3, has been determined by assembling the sequences of the physical map-based contigs of fosmid clones and of long polymerase chain reaction (PCR) products which were used for gap-filling. The entire length of the genome was 1,738,505 bp. The authenticity of the entire genome sequence was supported by restriction analysis of long PCR products, which were directly amplified from the genomic DNA. As the potential protein-coding regions, a total of 2061 open reading frames (ORFs) were assigned, and by similarity search against public databases, 406 (19.7%) were related to genes with putative function and 453 (22.0%) to the sequences registered but with unknown function. The remaining 1202 ORFs (58.3%) did not show any significant similarity to the sequences in the databases. Sequence comparison among the assigned ORFs in the genome provided evidence that a considerable number of ORFs were generated by sequence duplication. By similarity search, 11 ORFs were assumed to contain the intein elements. The RNA genes identified were a single 16S-23S rRNA operon, two 5S rRNA genes and 46 tRNA genes including two with the intron structure. All the assigned ORFs and RNA coding regions occupied 91.25% of the whole genome. The data presented in this paper are available on the internet at
ESTHER : Kawarabayasi_1998_DNA.Res_5_55
PubMedSearch : Kawarabayasi_1998_DNA.Res_5_55
PubMedID: 9679194
Gene_locus related to this paper: pyrho-PH0594 , pyrho-PH0863 , pyrho-PH1262

Title : beta-Galactosidase-neuraminidase deficiency in adults: deficiency of a freeze-labile neuraminidase in leukocytes and fibroblasts - Suzuki_1981_Hum.Genet_58_387
Author(s) : Suzuki Y , Sakuraba H , Potier M , Akagi M , Sakai M , Beppu H
Ref : Hum Genet , 58 :387 , 1981
Abstract : 4-methylumbelliferyl neuraminidase activity was studied in fibroblasts, leukocytes, and frozen tissues from adult patients with beta-galactosidase-neuraminidase deficiency and specific clinical manifestations. This enzyme was almost completely deficient in fibroblasts, but the residual activity was relatively high (20% of the control mean) in the leukocytes from the patients. The frozen liver from one patient showed the enzyme activity as high as controls. This enzyme consisted of two components, freeze-labile and freeze-stable, and it was demonstrated that only the labile enzyme was deficient in fibroblasts and leukocytes. The apparently normal activity of neuraminidase in frozen autopsy tissues of a patient may be explained by the loss of the labile component in control tissues after a long-term freezing. The neuraminidase activity was variable in parents and no definite conclusion was drawn on the hereditary nature of the disease.
ESTHER : Suzuki_1981_Hum.Genet_58_387
PubMedSearch : Suzuki_1981_Hum.Genet_58_387
PubMedID: 7327559
Gene_locus related to this paper: human-CTSA

Title : Hydrolysis of acetylthiocholine and butyrylthiocholine by cholinesterases of insects and a mite -
Author(s) : Sakai M
Ref : Appl Entomol Zool , 2 :111 , 1967